Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening

Rabe, Christina ; Bittner, Tobias ; Jethwa, Alexander ; Suridjan, Ivonne ; Manuilova, Ekaterina ; Friesenhahn, Michel ; Stomrud, Erik LU orcid ; Zetterberg, Henrik LU ; Blennow, Kaj LU and Hansson, Oskar LU orcid (2023) In Alzheimer's and Dementia 19(4). p.1393-1402
Abstract

Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ42/Aβ40 for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ42/Aβ40 evaluated the actionability of plasma Aβ42/Aβ40, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ42/Aβ40... (More)

Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ42/Aβ40 for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ42/Aβ40 evaluated the actionability of plasma Aβ42/Aβ40, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ42/Aβ40 could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ42 and/or Aβ40 cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion: Implementing plasma Aβ42/Aβ40 for routine clinical use may pose significant challenges, with misclassification risks. Highlights: Plasma Aβ42/Aβ40 ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ42/Aβ40 had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid, biomarkers, blood biomarkers, prescreening
in
Alzheimer's and Dementia
volume
19
issue
4
pages
1393 - 1402
publisher
Wiley
external identifiers
  • scopus:85139000666
  • pmid:36150024
ISSN
1552-5260
DOI
10.1002/alz.12801
language
English
LU publication?
yes
id
d04a1fa4-24c8-4f10-b40f-55c94971b79a
date added to LUP
2022-12-22 09:44:01
date last changed
2024-04-15 00:02:51
@article{d04a1fa4-24c8-4f10-b40f-55c94971b79a,
  abstract     = {{<p>Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> evaluated the actionability of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub>, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ<sub>42</sub> and/or Aβ<sub>40</sub> cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion: Implementing plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> for routine clinical use may pose significant challenges, with misclassification risks. Highlights: Plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.</p>}},
  author       = {{Rabe, Christina and Bittner, Tobias and Jethwa, Alexander and Suridjan, Ivonne and Manuilova, Ekaterina and Friesenhahn, Michel and Stomrud, Erik and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; amyloid; biomarkers; blood biomarkers; prescreening}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1393--1402}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Clinical performance and robustness evaluation of plasma amyloid-β<sub>42/40</sub> prescreening}},
  url          = {{http://dx.doi.org/10.1002/alz.12801}},
  doi          = {{10.1002/alz.12801}},
  volume       = {{19}},
  year         = {{2023}},
}